amino acids. The peptides that result from endopeptidase activity are then acted on by pancreatic ectopeptidases. These enzymes cleave single amino acids from the end of a peptide chain, and those present in pancreatic juice are specific for either neutral (carboxypeptidase A) or basic (carboxypeptidase B) amino acids situated at the C-terminus. Thus the products that result after digestion of a protein meal by gastric and pancreatic secretions include neutral and basic amino acids, as well as short peptides that have acidic amino acids at their C-termini and thus are resistant to carboxypeptidase A or
B (Fig. 30.13
The final phase of protein digestion takes place at the brush border. Mature enterocytes express a variety of peptidases on their brush borders, including both amino-peptidases and carboxypeptidases that generate products suitable for uptake across the apical membrane (see
Fig.
30.11 ). However, it should be noted that even with the substantial complement of active proteolytic enzymes, some dietary peptides are either relatively or totally resistant to hydrolysis. In particular, peptides containing either proline or glycine are digested very slowly. Fortunately the intestine can take up short peptides in addition to single amino acids. The majority of peptides taken up into the enterocyte in their intact form are then subjected to a final stage of digestion in the cytosol of the enterocyte to liberate their constituent amino acids for use in the cell or elsewhere in the body (Fig. 30.14 ). However, some di-and tripeptides may also be transported into the blood in their intact form.
•Fig. 30.13 Luminaldigestionofpeptidesresultingfrompartialproteolysisinthestomach.AA,aminoacid.(RedrawnfromBarrettKE.Gastrointestinal Physiology. NewYork:McGraw-Hill;2006.)Peptide with C-terminal neutral AA Carboxypeptidase AChymotrypsin Elastase Large peptides Trypsin Peptide with C-terminal basic AA Short peptides free neutral and basic AAs SerArg Carboxypeptidase B Ser Arg •Fig. 30.14 Awidevarietyofdipeptidesandtripeptidesaretakenupacrossthebrushbordermembranebytheproton-coupledsymporterknownaspeptide transporter 1 (PepT1).Theprotongradientiscreatedbytheactionofsodium/hydrogenexchangers(NHEs)intheapicalmembrane.Peptidesarelargelydigestedinthecytosoltotheirconstituentaminoacidsforexporttothebody,butasmallproportionmaybeexportedintact.
Uptake of Peptides and Amino Acids
The body is also endowed with a series of plasma membrane transporters capable of promoting uptake of the water-soluble products of protein digestion. Given the large number of amino acids, there is a relatively large number of specific transporters (see
Figs. 30.11 30.14 ). Amino acid transporters are of clinical interest because their absence in a variety of genetic disorders results in diminished ability to transport the relevant amino acid or acids. However, such mutations are often clinically silent, at least from a nutritional standpoint, because the amino acid in question can be assimilated by other transporters with overlapping specificity or in the form of peptides. This does not rule out the possibility of pathology in other organ systems in